Radiation treatment using x-ray source

ABSTRACT

Methods and apparatus are described for irradiating living tissue via a cavity or lumen, using an inflatable balloon applicator. In a preferred embodiment the applicator balloon has a balloon skin with x-ray contrast material in relatively low concentration, so that an outline of the balloon will appear sharply when imaged externally. In another preferred embodiment the balloon catheter has a drain for withdrawing liquids from the cavity, which may include channels or texture on the exterior of the balloon. Methods are described for using a switchable miniature x-ray tube, variable as to voltage and current, to achieve accuracy in an isodose profile.

BACKGROUND OF THE INVENTION

This application is a continuation in part of application Ser. No.10,683,885, filed Oct. 13, 2003, now

This invention concerns therapeutic radiation treatment of livingtissue, usually but not necessarily within a body cavity, which may be asurgical cavity following a resection of a tumor. In one aspect theinvention is concerned with use of a switchable, miniature electronicx-ray source, which may be controllable as to depth and intensity, foradministering such therapeutic treatment.

Treatment of surgical cavities, such as after malignant tumor excision,has been accomplished with applicators which are inserted usually into anewly formed opening through the skin, a conveniently located openinginto the surgical resection cavity. Generally the location is differentfrom the surgical closure itself. Applicators have been disclosed whichessentially comprise a balloon of known and relatively rigid geometry,essentially spherical, expandable generally to about four to sixcentimeters, that is, designed to have an inflated size of about four tosix centimeters diameter. Some of the generally spherical ballooncatheters were described as having multiple walls to form inner andouter spaces, for reasons relating to the objective of delivering auniform dose to tissue surrounding the balloon. In the prior art suchknown-geometry balloons were inflated with a liquid, with an applicatorguide positioned within the balloon and in the liquid, so that theapplicator guide could receive a radiation source comprising aradioactive isotope.

With balloons limited to known geometries, there are limitations in theability to treat a cavity margin thoroughly. In some cases, the patientcannot take advantage of such a treatment protocol because theknown-geometry balloon applicator simply cannot fill many surgicalcavities that are irregular in shape. Other measures have to be used inthose cases, such as external radiation therapy.

Another limitation of known procedures using balloon catheters is inregard to locating the balloon correctly within a cavity of the patient,such as a resection cavity. The saline solution used to inflate theballoon contains contrast material which will be visible by taking anexternal x-ray. With the contrast material contained in the balloon'ssolution, the surgeon or technician can detect a pale “shadow” in thex-ray to determine the location of the balloon and to correct itsposition if needed. The procedure typically calls for use of thecontrast material at about 3% in the saline solution. Dose planning forthe known-geometry balloon is based on specific concentration ofcontrast. However, because the balloon shape is difficult to see in thex-ray, surgeons usually add the contrast material in a much higherconcentration, not as contemplated by the dose plan, so as to betterdetect the balloon in the x-ray. The concentration may be up to about20%-30% in practice. As a result, the therapeutic radiation from thex-ray source placed into the center of the balloon becomes attenuated tothe extent that the actual dose profile received in a patient's tissuemay be significantly less than the prescribed dose.

The use of isotopes has been the practice in administering x-rayradiation to patients prior to the present invention. The isotopes mustbe handled carefully and reliably shielded between uses. With theisotopes they are always “on”, and only one setting is available for alldwell locations where a dose is to be administered. In many cases itwould be convenient to have a better procedure and source that wouldallow modulation and more accurate dose delivery.

SUMMARY OF THE INVENTION

The invention now disclosed provides improved procedures for therapeuticradiation treatment of tissue, which may be following resection of atumor or which may involve administering the radiation within anexisting body cavity or in other locations. Although isotopes can beused in some of the procedures of the invention, in some, the radiationis emitted from an electronic switchable x-ray source that can bemodulated as to dose depth, via voltage in the x-ray source, andpreferably also as to intensity, via current in the x-ray source. In apreferred form the source is a miniature x-ray tube, having a diameteron the order of roughly about ½-3 mm, and a length of about 5-15 mm.

Pursuant to the invention a miniature x-ray tube is inserted into aballoon catheter, either before or after the balloon has been placed atthe desired location in the patient. The x-ray source is switched on viaa control unit outside the patient only when the balloon has beeninserted, inflated and confirmed as to position, and with the patientand physician ready to administer the prescribed dose profile to thepatient. Radiation dose delivery can be high compared to prior practice,about 5 to 50 Gy/hour. The x-ray source can operate in the range ofabout 40 kVp to 80 kVp.

In another aspect of the invention, either a switchable x-ray source oran isotope can be used in a therapeutic radiation treatment procedure.The balloon of the catheter is doped with contrast medium, in or on theskin of the balloon. The inflation medium for the balloon, which may bea saline solution, need not have any contrast medium added. The ballooncatheter is placed in a cavity of living tissue, i.e. in a patient, andthe balloon is inflated and then verified as to position in the cavity.This can be done by an x-ray taken exteriorly to the patient, since theballoon skin with contrast medium will have its outline visible byx-ray, after which the position of the balloon can be adjusted, ifnecessary. Once the correct balloon position has been verified byexternal imaging, the x-ray source, which may be an isotope source or aswitchable source, is placed in the balloon catheter (if a switchabletube the source can be placed in the balloon before insertion). Thesource preferably is moved through a series of positions within theballoon catheter to administer radiation to tissue adjacent to theballoon, in accordance with a prescribed dose profile.

The use of a balloon catheter with contrast medium in or on the skin ofthe balloon, as opposed to being contained in a saline solution withinthe balloon, is a strong departure from the prior art. The advantage isthat the physician will not over-dope the saline solution with contrastmedium, thus maintaining the strength of the therapeutic radiationemitted from inside the balloon. The balloon wall has virtually noattenuating effect on the therapeutic radiation, when the radiationpasses through the balloon in a normal or generally normal direction tothe skin of the balloon. However, when the x-ray is taken from outside,the outline of the balloon will show up sharply because of thetangential direction of viewing that outline and the fact that theoutline represents many times the wall thickness of the balloon, perhaps20-40 times the density of contrast medium, thus contributing to thevisible outline in the x-ray.

DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a catheter device of the invention with an inflatableballoon applicator within which is an x-ray source, shown at a cutawayof the balloon.

FIG. 2 schematically shows the device of FIG. 1 with the ballooninserted in a cavity of a patient's body and inflated.

FIGS. 3 and 3A are a schematic elevation showing the device in apatient's breast; and a graph indicating modulation of dose depth forx-rays from a switchable x-ray source for the situation of FIG. 3 atdifferent positions, in accordance with a dose prescription and takinginto account adjacent organs and tissues.

FIGS. 4 and 4A are a schematic similar to FIG. 3; and a graph showing anaspect of dose modulation, in this case modulation of dose intensity bymodulating current in the x-ray tube, for different positions as shownin FIG. 4.

FIGS. 5A, 5B and 5C show the catheter and the components of the catheterof the invention in greater detail.

FIG. 6 schematically indicates the balloon of the catheter in crosssection, as it is x-rayed from the exterior of a patient, with a graphindicating generally the attenuation of x-rays as a function of positionon the balloon.

FIG. 7 is a graph indicating path length for x-rays passing through theballoon as in FIG. 7.

DESCRIPTION OF PREFERRED EMBODIMENTS

In the drawings, FIG. 1 shows somewhat schematically an applicator 10according to one embodiment of the invention, the applicator including aflexible control line or cable 12 leading from a controller, not shown,and a catheter or applicator portion 14. A balloon 16 of the applicatorand catheter is shown inflated in FIG. 1. The applicator device isgenerally as shown in co-pending application Ser. No. 10/683,885, filedOct. 13, 2003.

As shown, at the proximal end 18 of the applicator is a branch 20. Thethree ports 22, 24 and 26 of this branch device may comprise a serviceport, a drainage port and a balloon inflation port, respectively. Thefunctions of these ports are explained further below with reference toother drawings.

A flexible main shaft 28 extends from the branch device 20 to theballoon 16, and is sealed to the balloon at 30. The balloon in FIG. 1 isshown partially cut away to reveal an electronic x-ray source 32 withinthe balloon, at the end of the control line 12 and moveablelongitudinally within the balloon 16 and catheter 10. In preferredembodiments the x-ray tube 32 is less than 4 mm in diameter, preferablyno greater than about 3 to 3.2 mm in diameter, and in some embodimentsthis tube is as small as 1 mm in diameter or even smaller.

The shaft 28 is flexible, and may be highly flexible and pliable nearthe proximal end 18, as explained in the co-pending applicationreferenced above, for the purpose of folding the applicator over againstthe breast when not in use, when the control line 12 and x-ray source 32are not inserted into the applicator, particularly for breastirradiation involving several dose fractions such that the applicatorneed not be removed between fractions.

The flexible shaft provides a lumen for admitting a fluid to inflate theballoon 16, while also providing a duct or lumen for insertion of theradiation source 12, via guides connected to the balloon. The shaft 24also preferably provides a channel for drainage of liquids from the bodycavity within which the applicator is inserted. A drainage receptaclecan be connected to the end of the drainage port or an aspirator can beused when needed to withdraw liquids. The applicator 10 is shownschematically in FIGS. 2, 3 and 4 as inserted into a resection cavity ofa breast for treatment.

FIGS. 5A, 5B and 5C show the applicator 10 in greater detail, and withthe balloon 16 deflated and collapsed. The service port 22, in line withthe flexible shaft 28, as well as the drainage port 24 and the ballooninflation port 26, are illustrated. Also shown is a distance scalepreferably included, with distances shown at 6 cm, 7 cm, 8 cm, etc., upto about 15 cm, to indicate to the physician the total depth of theapplicator into cavity and opening wound. This provides a direct andeasily used means to determine the position of the distal end 35 of theapplicator as it is being inserted. As shown in FIGS. 5B and 5C,drainage is provided for the resection cavity via drain holes 36 at thedistal end 35 of the applicator, beyond the balloon 16, communicatinginternally to the drain port 24, and also preferably via drain holes 38shown just proximal of the balloon, for draining fluids which travelover the surface of the balloon. As in co-pending application Ser. No.10/683,885, the balloon preferably has some form of liquid channelingmeans on its outer surface. This could be a multiplicity of bumps,allowing for liquid travel even though the balloon is engaged againstthe tissue, or a series of longitudinal ridges on the balloon surface toform channels. The drain holes 38 catch most of the liquid flowing inthis manner, and these holes communicate with the drain port 24.

The balloon 16 may advantageously be formed of a silicone material,although other appropriate biocompatible materials can be used. Theballoon material is bonded to the outside surface of the flexible shaft28 in sealed relationship thereto, by known procedures.

FIGS. 2, 3 and 4 indicate somewhat schematically the use of theapplicator device 10 in a resection cavity of a human breast 41, forradiation therapy. In FIG. 2 the catheter 10 is shown with its balloon16 shown in dashed lines, and the shaft 28 in the balloon forming aguide for an x-ray source which may either be a miniature x-ray tube oran isotope. A seal 40 is shown in FIG. 2, for sealing the flexible shaft28 of the catheter/applicator against the surface of the skin where itenters the body. Also shown in FIG. 2 is a connector 42 for connectingthe applicator shaft, via the service port 22, to an exterior cable 44that contains the control cable 12, leading to the controller (notshown) for the applicator and for the x-ray source, if the source is acontrollable miniature tube.

FIGS. 3 and 3A illustrate the ability of the invention to achieve a moreexact dose profile by use of a miniature electronic x-ray source in theapplicator 10, a source which is capable of voltage variation and thusvariation of the depth of dose. As one rather simple example, four dwellpositions are shown in FIG. 3 and represented in a bar graph in FIG. 3A.The deepest dwell position, position 1, is closest to the lungs of thepatient. Thus, the voltage is relatively low for this dwell position,controlling the depth of penetration into the surrounding tissue suchthat radiation will not reach the lungs to any appreciable degree.

The second dwell position is farther from the lungs, and FIG. 3A showsthat the voltage is increased for this dwell position, for a greaterdepth of penetration. Similarly, dwell positions 3 and 4 areprogressively farther from the lungs and the voltage and depth of doseare progressively higher.

FIGS. 4 and 4A illustrate schematically the use of a switchable,controllable electronic x-ray source in the catheter 10, wherein currentis varied at different dwell positions in order to vary the doseintensity at different positions. In the schematic drawing of FIG. 4,four different dwell positions are again indicated for the electronicx-ray source, within the balloon 16 of the catheter 10, the balloonpositioned in a resection cavity in a patient's breast 41. The controlcurrent does not vary the depth of penetration of the radiation, onlythe dose intensity. In the illustrated procedure, the current is variedin order to produce a uniform isodose profile. Thus, at positions 1 and4 where the x-ray source is closest to tissue, the current is set at alower level, while at dwell positions 2 and 3, close to the center ofthe balloon 16 and of the resection cavity, where the tube is moredistant from tissue, the current is set higher. Note that dose intensitycan be controlled also by controlling the length of time the source is“on” at each dwell position, or simply by controlling the length ofdwell at each position assuming the source remains “on”. These profilesof FIGS. 4 to 5A are just examples of how the variation of voltage andcurrent using an electronic x-ray source can be beneficially usedaccurately to create a required isodose profile.

FIGS. 6 and 7 illustrate the balloon 16 having an x-ray contrast mediumin or on the balloon wall. As explained above, this differs from priorpractice in which a saline solution within the balloon contained a weaksolution of contrast medium so that the balloon would show up inexternal x-ray imaging, for location of the balloon. In this case thecontrast medium is only in or on the balloon wall, and this medium willabsorb radiation, indicated at 46, during external imaging; it will alsoabsorb radiation from the therapeutic source and thus will attenuate theradiation delivered from inside the balloon to some extent. However,with a low concentration of such contrast medium in the balloon wall,the attenuating effect of the medium for radiation passing through theballoon at an angle normal or generally normal to the balloon wall willbe small and essentially negligible. On the other hand, the effect ofradiation, particularly x-ray radiation, passing tangentially throughthe edges of the balloon as indicated in FIGS. 6 and 7, will be at amaximum, since the radiation must pass through the balloon edge wise atthis tangential angle, a much longer effective path length. The resultis that a balloon 16 with such contrast medium can be located byexternal x-ray, visible in an x-ray image by its edges. This isdemonstrated in FIG. 7 showing effective path length of x-rays throughballoon material as a function of distance from the center of theballoon. The densest outline of the balloon will be at itscircumference, especially at distal and proximal ends of the balloonitself, where the wall material may be somewhat thicker at itsattachment to the flexible shaft 28 and in any event, where the balloonhas areas that are stretched far less due to the geometry of the balloonand its attachment to the flexible shaft 28 of the catheter device.

FIG. 6 shows in a schematic approximation a graph of x-ray density(darkness or density of the line appearing in an x-ray image) on avertical axis, versus position. For clarity the balloon 16 isrepresented directly adjacent to the graph, and showing the direction ofx-ray radiation 46. As illustrated, density is low in the x-ray image ofthe balloon at a region 48 in FIG. 6 where the radiation passesgenerally normally through the balloon wall; however, spikes of extremedensity are shown at 50 and 52, where the rays must pass throughconsiderable distance of the balloon wall on edge. As can be seen fromthe graph of FIG. 7 (showing effective path length through both 4 and 5cm diameter balloons), the effective path length at these tangentregions can be about 15 to 25 times greater than the normal path length.Thus, the contrast-doped balloon wall provides a far superior imagingarrangement than the prior saline solution, without adversely affectingtherapeutic radiation.

The procedures and apparatus described above are applicable to naturalbody cavities (e.g., bladder, uterus, vaginal), and naturally occurringlumens, as well as surgically created cavities. The term cavity in theclaims is intended broadly to refer to natural or surgical cavities orlumens. Also, except where a switchable x-ray source is specificallycalled for herein for the advantages it offers in modulation or otherpurposes, the described procedures can ordinarily be performed usingisotopes. The term brachytherapy device refers to either type ofradiation source.

The above described preferred embodiments are intended to illustrate theprinciples of the invention, but not to limit its scope. Otherembodiments and variations to these preferred embodiments will beapparent to those skilled in the art and may be made without departingfrom the spirit and scope of the invention as defined in the followingclaims.

1. A method for irradiating living tissue using a balloon catheter,comprising: placing the balloon catheter in a cavity of the livingtissue, inflating the balloon catheter, and verifying the balloonplacement by x-ray taken exterior to the patient, the balloon catheterhaving a balloon wall adjacent to tissue to be irradiated, and theballoon wall having an x-ray contrast material, thus enabling visualdetection of an outline of the balloon using the exterior x-ray,positioning a switchable x-ray source at a desired position in theballoon catheter, and moving the source through a series of positionswithin the balloon catheter, to administer radiation to tissue adjacentto the balloon.
 2. The method of claim 1, wherein the step of moving theswitchable x-ray source comprises stepping the position of the x-raysource through a series of distinct dwell positions, and turning thex-ray source on at each dwell position and off between dwell positions.3. The method of claim 1, further including modulating x-ray dose depthat different positions within the balloon catheter by adjusting voltagein the switchable x-ray source, and adjusting intensity of x-rays duringthe treatment in accordance with a dose prescription, as the source ismoved through the cavity.
 4. The method of claim 1, including the stepsof placing the x-ray source into the balloon catheter within the cavityand removing the x-ray source in a plurality of iterations for a seriesof dose fractions over a treatment period which may extend over severaldays.
 5. The method of claim 1, wherein the balloon is generallyspherical in shape.
 6. The method of claim 1, wherein the balloon isgenerally ellipsoidal in shape.
 7. The method of claim 1, wherein theballoon is generally hotdog shaped.
 8. The method of claim 1, whereinthe cavity in the tissue is irregularly shaped, and wherein the balloonis shaped to match the cavity.
 9. The method of claim 1, includingadministering x-ray dose from the switchable x-ray source at about 5-50Gy per hour.
 10. The method of claim 1, wherein the switchable x-raysource is operated at greater than about 40 kV_(p).
 11. The method ofclaim 1, wherein the switchable x-ray source is operated at about 40kV_(p) to 80 kV_(p).
 12. The method of claim 1, wherein, duringtreatment using the switchable x-ray source, the x-ray source ismodulated in intensity of radiation by modulating current in the x-raysource to accurately achieve a prescribed isodose profile.
 13. Themethod of claim 12, further including modulating x-ray dose depth atdifferent positions within the balloon catheter by adjusting voltage inthe switchable x-ray source.
 14. A method for irradiating living tissueusing a balloon catheter, comprising: placing the balloon catheter in acavity of the living tissue, and inflating the balloon catheter,positioning a switchable x-ray source at a desired position in theballoon catheter, switching on the x-ray source, and moving the sourcethrough a series of positions within the balloon catheter, to administerradiation to tissue adjacent to the balloon.
 15. The method of claim 14,wherein the step of moving the switchable x-ray source comprisesstepping the position of the x-ray source through a series of distinctdwell positions, and turning the x-ray source on at each dwell positionand off between dwell positions.
 16. The method of claim 14, wherein thestep of moving the x-ray source comprises moving the source continuouslywhile modulating radiation from the x-ray source by at least one of: (a)switching the x-ray source on and off, (b) varying current in the x-raysource to modulate dose intensity, and (c) varying voltage in the x-raysource to modulate x-ray dose depth at different positions.
 17. Themethod of claim 14, further including modulating x-ray dose depth atdifferent positions within the balloon catheter by adjusting voltage inthe switchable x-ray source, and adjusting intensity of x-rays duringthe treatment in accordance with a dose prescription, as the source ismoved through the cavity.
 18. The method of claim 14, wherein the stepof moving the switchable x-ray source comprises stepping the position ofthe x-ray source through a series of distinct dwell positions, andmodulating radiation from the x-ray source at different positions by atleast one of: (a) switching the x-ray source on and off, (b) varyingcurrent in the x-ray source to modulate dose intensity, and (c) varyingvoltage in the x-ray source to modulate x-ray dose depth.
 19. The methodof claim 18, including the steps of placing the x-ray source into theballoon catheter within the cavity and removing the x-ray source in aplurality of iterations for a series of dose fractions over a treatmentperiod which may extend over several days.
 20. The method of claim 14,including the steps of placing the x-ray source into the ballooncatheter within the cavity and removing the x-ray source in a pluralityof iterations for a series of dose fractions over a treatment periodwhich may extend over several days.
 21. The method of claim 14, whereinthe balloon is generally spherical in shape.
 22. The method of claim 14,wherein the balloon is generally ellipsoidal in shape.
 23. The method ofclaim 14, wherein the balloon is generally hotdog shaped.
 24. The methodof claim 14, including administering x-ray dose from the switchablex-ray source at about 5-50 Gy per hour.
 25. The method of claim 14,wherein the switchable x-ray source is operated at greater than about 40kV_(p).
 26. The method of claim 14, wherein the switchable x-ray sourceis operated at about 40 kV_(p) to 80 kV_(p).
 27. The method of claim 14,further including draining liquids from the cavity of the living tissuewhile the inflated balloon is within the cavity, using drain lumensformed in the catheter and extending to exterior of the tissue.
 28. Themethod of claim 27, wherein the balloon wall has an exterior surfacewith texture to define drain channels to provide a path for flow ofliquids toward the exterior of the cavity.
 29. The method of claim 28,wherein the balloon catheter has a generally central flexible shafthaving drain holes in a distal end of the shaft, distal of the balloon,connected to the drain lumens which pass through the shaft, and furtherincluding drain holes in the exterior of the shaft proximal of theballoon for collecting liquids traveling over the surface of theballoon.
 30. A method for applying therapeutic radiation to livingtissue using a balloon catheter, comprising: inserting into a cavity ofthe living tissue, through an entry point on a patient, a catheterincluding an inflatable balloon having a balloon skin containing acontrast medium that will partially block radiation from an externalimaging device, and including a guide in the balloon, inflating theballoon in the cavity, performing an external imaging of the balloon toverify the location of the balloon within the cavity by revealing anoutline of the balloon via the contrast medium in the balloon skin, andadjusting the position of the balloon by reference to the external imageif necessary, positioning a brachytherapy device at a desired positionwithin the balloon, via the guide of the catheter, and administering adesired radiation dose from the brachytherapy device in accordance witha dose prescription.
 31. The method of claim 30, further includingmoving the brachytherapy device through multiple locations along acentral access of the balloon to obtain an isodose profile as desiredper the prescription, then removing the brachytherapy device and theballoon catheter from the cavity.
 32. The method of claim 31, furtherincluding repeating the step of administering radiation therapy inmultiple therapy fractions in accordance with the prescription.
 33. Themethod of claim 30, wherein the brachytherapy device includes aradioactive isotope.
 34. The method of claim 30, wherein thebrachytherapy device comprises a switchable x-ray tube.
 35. The methodof claim 34, including inserting the brachytherapy device into theballoon prior to insertion of the balloon into the resection cavity. 36.The method of claim 30, further including draining liquids from thecavity of the living tissue while the inflated balloon is within thecavity, using drain lumens formed in the catheter and extending toexterior of the tissue.
 37. The method of claim 36, wherein the balloonwall has an exterior surface with texture to define drain channels toprovide a path for flow of liquids toward the exterior of the cavity.38. The method of claim 37, wherein the balloon catheter has a generallycentral flexible shaft having drain holes in a distal end of the shaft,distal of the balloon, connected to the drain lumens which pass throughthe shaft, and further including drain holes in the exterior of theshaft proximal of the balloon for collecting liquids traveling over thesurface of the balloon.
 39. The method of claim 30, includingadministering x-ray does from the brachytherapy device at about 5-50 Gyper hour.
 40. A method for applying therapeutic radiation to livingtissue using a balloon catheter, comprising: inserting into a cavity ofthe living tissue through an entry point on a patient, a catheterincluding an inflatable balloon and including a guide in the balloon,inflating the balloon in the cavity, positioning a brachytherapy deviceat a desired position within the balloon, via the guide of the catheter,administering a desired radiation dose from the brachytherapy device inaccordance with a dose prescription, and draining liquids from thecavity of the living tissue while the inflated balloon is within thecavity, using drain lumens formed in the catheter and extending toexterior of the tissue.
 41. The method of claim 40, wherein the balloonwall has an exterior surface with texture to define drain channels toprovide a path for flow of liquids toward the exterior of the cavity.42. The method of claim 41, wherein the balloon catheter has a generallycentral flexible shaft having drain holes in a distal end of the shaft,distal of the balloon, connected to the drain lumens which pass throughthe shaft, and further including drain holes in the exterior of theshaft proximal of the balloon for collecting liquids traveling over thesurface of the balloon.
 43. The method of claim 41, includingadministering x-ray does from the brachytherapy device at about 5-50 Gyper hour